Despite considerable progress using surgery, chemotherapy, and radiation to treat cancer, the 5-year survival rate for many cancers is still very low. An immune response directed to cancer cells may limit cancer development. However, tumor-mediated immunosuppression often blocks these antitumor responses. Therefore, a novel option suggested for treating cancer is to stimulate an effective immune response against tumor cells.
In the art, the possibility of using microorganisms as powerful adjuvants in the arsenal of anti-cancer immunotherapy has been recognized. Recent works highlighted the value of using attenuated microorganisms including virus, bacteria and parasites for treating cancer. For example, attenuated herpes virus expressing GM-CSF genetically modified to target tumor cells has been approved by the FDA for the treatment of metastatic melanomas (Amgen, IMLYGIC®). Moreover, attenuated microorganisms associated with another medicine are under clinical evaluation. For example, Opdivo® (nivolumab, IgG4 anti-PD1) associated to an attenuated bacterium Listeria monocytogenes is under clinical evaluation as an immunotherapy against non-small cell lung cancer. The combination of an attenuated virus modified to express antigens E6 and E7 from the human papillomavirus HPV16 (TG4001) with avelumab (IgG1 anti-PD-L1) is evaluated in phase 1-2 in the treatment of the head and neck cancers positives for HPV. Listeria monocytogenes that expresses mesotheline (CRS-207) associated with pembrolizumab (IgG4 anti-PD-1) is evaluated in phase 1 for the treatment of the gastric cancers.
Neospora caninum is an obligate intracellular protozoan parasite responsible for bovine neosporosis. Despite being taxonomically close to Toxoplasma gondii, Neospora caninum presents significant differences with this protozoan parasite. In particular,
Neospora caninum does not infect humans The life cycle of Neospora caninum is characterized by two distinct phases: (i) a sexual phase in the final host (canids and dogs in particular) which leads to the production of oocysts, container of the sporozoites, eliminated in deposit and (ii) an asexual phase in an intermediate host (such as, for example, sheep, goats, cattle, equidae, etc.) who leads to the production of tachyzoites, and then of cysts containing bradyzoites. The invasion process of the host cells by Neospora caninum comprises several stages leading to the formation of a parasitophorous vacuole in which the parasite multiplies and develops. Active entry and vacuole formation result from the coordinated secretion of parasite secretory organelles including rhoptries (ROP) and dense granules (GRA). The contents of these organelles are sequentially released during the lytic cycle and play a crucial role in the host-parasite interactions.
The inventors surprisingly showed that the administration of at least one strain of Neospora caninum to a subject induces a strong immune response, in particular against tumors. The present invention thus aims at providing a new treatment for cancer or infectious diseases based on the use of Neospora caninum. 